Understanding the life cycle of HIV could provide big contribution towards the development of therapeutic strategies to treat AIDS. The inhibition of HIV replication may allow the blockage of the process resulting in the retardation of HIV's attack on our immune system. p21, the most significant cyclin kinase inhibitor should play a significant role in the inhibition of HIV replication. In fact, recent studies with "elite controllers," which are a small subset of AIDS patients in whom levels of HIV replication is not detectable without any antiviral treatment is shown to be due to increased p21 expression. Increased p21 expression results in a significantly reduced ability of CD4 T cells from elite controllers to support HIV-1 replication, where it may directly interact with incoming HIV to inhibit its replication or it exerts a post replication effect to prevent infection., p21-mediated restriction of HIV-1 may have numerous advantages: Specifically, p21 does not directly interact with HIV-1 proteins, but instead inhibits the host protein CDK9 that is required for HIV-1 replication; this indirect restriction of HIV-1 replication may be less susceptible to viral mutational escape. Up regulation of p21 in CD4 T cells from elite controllers alters proliferation and activation of CD4 T cells to reduce the susceptibility to HIV-1 infection. It may also be possible that the ability of p21 to inhibit HIV-1 replication might also contribute to the maintenance of transcriptionally silent HIV-1 DNA in latently infected T cells. If this is true then targeting p21 will provide novel strategy to manipulate as well as reactivate viral gene expression from CD4 T cells with latent infection. This process will have potential to decrease long-term viral persistence in the presence of antiretroviral therapy. Therefore, a detailed investigation of the p21 interactions in HIV-1 infection will assist designing therapeutic strategies to increase host resistance to HIV-1. This study based on our experience with recombinant p21 protein on immune system; hypothesize the protective/therapeutic role of endogenous and exogenous p21 with respect to in vitro and in vivo HIV infection in AIDS patients.
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